title: Morphine could increase apoptotic factors in the nucleus accumbens and prefrontal cortex of rat brain's reward circuitry.
abstract: The nucleus accumbens (NAc) and prefrontal cortex (PFC) are two parts of neuronal reward circuit involved in motivated and goal-directed behaviors. Some data suggest that morphine is toxic to neurons and induces apoptosis, while other evidence shows that morphine could have beneficial effects against cell death. This study was designed to evaluate the effect of morphine on apoptosis by measuring the expression of apoptotic proteins in two important regions, the NAc and PFC, in the rat brain's reward circuitry. Morphine subchronic administration in different doses (0.5, 5 and 10mg/kg) in conditioned place preference (CPP) paradigm (3 times in 3 days, for each dose in each group of rats) was used to induce its rewarding effect. Then, the expression of four apoptotic factors; Bax, Bcl2, caspase3 and PARP, in the NAc and PFC were assessed using the Western blot technique. All of morphine-treated groups showed increase of apoptotic factors in these regions. In the NAc, morphine significantly increased the Bax/Bcl-2 ratio, caspase3 and PARP in the lowest dose (0.5mg/kg) but in the PFC considerable increase was seen in dose of 5mg/kg. Elevation of apoptotic factors in the NAc and PFC implies that morphine can affect the molecular mechanisms which interfere with apoptosis through different receptors. Our findings suggest that the NAc and PFC may have a different distribution of receptors which become active in different doses of morphine.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box 19615-1178, Tehran, Iran.
authors.forename: Seyedeh-Najmeh
authors.initials: SN
authors.lastname: Katebi
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Razavi
authors.forename: Shabnam
authors.initials: S
authors.lastname: Zeighamy Alamdary
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
authors.forename: Abbas
authors.initials: A
authors.lastname: Haghparast
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D003214:Conditioning, Classical / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000633:toxicity*; D009294:Narcotics / Q000633:toxicity*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D009294:Narcotics; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D009020:Morphine; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3
keywords: Apoptosis; Morphine; Nucleus accumbens; Prefrontal cortex; Reward; Western blot